High-grade tumours promote growth of other less-malignant tumours in the same prostate.

Prostate cancer is a multifocal disease, but if and how individual prostate tumours influence each other is largely unknown. We therefore explored signs of direct or indirect tumour-tumour interactions in experimental models and patient samples. Low-metastatic AT1 and high-metastatic MatLyLu (MLL) Dunning rat prostate cancer cells were injected into separate lobes of the ventral prostate of immunocompetent rats. AT1 tumours growing in the same prostate as MLL tumours had increased tumour size and proliferation compared to AT1 tumours growing alone. In addition, the vasculature and macrophage density surrounding the AT1 tumours were increased by MLL tumour closeness. In patient prostatectomy samples, selected to contain an index tumour (tumour with the highest grade, International Society of Urological Pathology (ISUP) grade 1, 2, 3 or 4) and a low-grade satellite tumour (ISUP grade 1), cell proliferation in low-grade satellite tumours gradually increased with increasing histological grade of the index tumour. The density of blood vessels and CD68+ macrophages also increased around the low-grade satellite tumour if a high-grade index tumour was present. This suggests that high-grade tumours, by changing the prostate microenvironment, may increase the aggressiveness of low-grade lesions in the organ. Future studies are needed to explore the mechanisms behind tumour-tumour interactions and their clinical importance. This article is protected by copyright. All rights reserved.

The Journal of pathology. 2020 Dec 17 [Epub ahead of print]

Sofia Halin Bergström, Stina Rudolfsson, Marie Lundholm, Andreas Josefsson, Pernilla Wikström, Anders Bergh

Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden., Department of Surgical and Perioperative Sciences, Urology, Umeå University, Umeå, Sweden.